Estimating maximal In vitro skin permeation flux from studies using non-sink receptor phase conditions
Date
2016
Authors
Yousef, S.
Liu, X.
Mostafa, A.
Mohammed, Y.
Grice, J.E.
Anissimov, Y.G.
Sakran, W.
Roberts, M.S.
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Journal article
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Pharmaceutical Research, 2016; 33(9):2180-2194
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Abstract
Purpose: This study explored the impact of non-sink receptor conditions on the in vitro skin permeation test (IVPT) and sought to estimate equivalent sink condition IVPT data. Methods: Simulated diffusion model and experimental IVPT data were generated for ethyl salicylate across human epidermal membranes in Franz diffusion cells using six different receptor phases, with a 10 fold variation in ethyl salicylate solubility. Results: Both simulated and experimental IVPT – time profiles were markedly affected by receptor phase solubility and receptor sampling rates. Similar sink condition equivalent estimated maximum fluxes were obtained by nonlinear regression and adjustment of linear regression estimates of steady state flux for relative saturation of the receptor phase over time for the four receptor phases in which the ethyl salicylate was relatively soluble. The markedly lower steady - state fluxes found for the other two phases in which ethyl salicylate was less soluble was attributed to an aqueous solution boundary layer effect. Conclusions: Non-sink receptor phase IVPT data can be used to derive equivalent sink receptor phase IVPT data provided the receptor phase solubility and hydrodynamics are sufficient to minimise the impact of aqueous diffusion layers on IVPT data.
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Copyright 2016 Springer Science+Business Media New York